PMID- 33589541
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 8
IP  - 2
DP  - 2021 Mar
TI  - Mass Cytometry of CSF Identifies an MS-Associated B-cell Population.
LID - 10.1212/NXI.0000000000000943 [doi]
LID - e943
AB  - OBJECTIVE: To identify an MS-specific immune cell population by deep immune 
      phenotyping and relate it to soluble signaling molecules in CSF. METHODS: We 
      analyzed surface expression of 22 markers in paired blood/CSF samples from 39 
      patients using mass cytometry (cytometry by time of flight). We also measured the 
      concentrations of 296 signaling molecules in CSF using proximity extension assay. 
      Results were analyzed using highly automated unsupervised algorithmic 
      informatics. RESULTS: Mass cytometry objectively identified a B-cell population 
      characterized by the expression of CD49d, CD69, CD27, CXCR3, and human leukocyte 
      antigen (HLA)-DR as clearly associated with MS. Concentrations of the B 
      cell-related factors, notably FCRL2, were increased in MS CSF, especially in 
      early stages of the disease. The B-cell trophic factor B cell activating factor 
      (BAFF) was decreased in MS. Proteins involved in neural plasticity were also 
      reduced in MS. CONCLUSION: When analyzed without a priori assumptions, both the 
      soluble and the cellular compartments of the CSF in MS were characterized by 
      markers related to B cells, and the strongest candidate for an MS-specific cell 
      type has a B-cell phenotype.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Johansson, David
AU  - Johansson D
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Rauld, Celine
AU  - Rauld C
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Roux, Julien
AU  - Roux J
AUID- ORCID: 0000-0002-4192-5099
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Regairaz, Camille
AU  - Regairaz C
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Galli, Edoardo
AU  - Galli E
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Callegari, Ilaria
AU  - Callegari I
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Raad, Layla
AU  - Raad L
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Waldt, Annick
AU  - Waldt A
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Cuttat, Rachel
AU  - Cuttat R
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Roma, Guglielmo
AU  - Roma G
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Diebold, Martin
AU  - Diebold M
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Becher, Burkhard
AU  - Becher B
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Kuhle, Jens
AU  - Kuhle J
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Derfuss, Tobias
AU  - Derfuss T
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Carballido, Jose M
AU  - Carballido JM
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland.
FAU - Sanderson, Nicholas S R
AU  - Sanderson NSR
AUID- ORCID: 0000-0001-6370-1961
AD  - From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., 
      N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes 
      for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); 
      Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental 
      Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., 
      M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and 
      University of Basel, Switzerland. nicholas.sanderson@unibas.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210215
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (Biomarkers)
RN  - 0 (TNFSF13B protein, human)
SB  - IM
MH  - Adult
MH  - B-Cell Activating Factor/*cerebrospinal fluid
MH  - B-Lymphocytes/*cytology/immunology
MH  - Biomarkers/analysis/*cerebrospinal fluid
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*immunology
MH  - Phenotype
PMC - PMC8057060
EDAT- 2021/02/17 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/02/15
CRDT- 2021/02/16 06:02
PHST- 2020/07/19 00:00 [received]
PHST- 2020/10/28 00:00 [accepted]
PHST- 2021/02/16 06:02 [entrez]
PHST- 2021/02/17 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/02/15 00:00 [pmc-release]
AID - 8/2/e943 [pii]
AID - NEURIMMINFL2020033860 [pii]
AID - 10.1212/NXI.0000000000000943 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2021 Feb 15;8(2):e943. doi: 
      10.1212/NXI.0000000000000943. Print 2021 Mar.